| Title: | Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles |
| Journal: | Nature Genetics |
| Published: | 3 Feb 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35115687/ |
| DOI: | https://doi.org/10.1038/s41588-021-00990-0 |
| URL: | https://www.nature.com/articles/s41588-021-00990-0.pdf |
| Citations: | 178 (137 in last 2 years) as of 8 Aug 2024 |
Publication 12567
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Abstract
Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.</p>
13 Keywords
- Alleles
- Cardiovascular System
- Case-Control Studies
- Central Nervous System
- Genetic Loci
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Migraine Disorders
- Migraine with Aura
- Molecular Sequence Annotation
- Polymorphism, Single Nucleotide
- Quantitative Trait Loci
71 Authors
- Heidi Hautakangas
- Bendik S. Winsvold
- Sanni E. Ruotsalainen
- Gyda Bjornsdottir
- Aster V. E. Harder
- Lisette J. A. Kogelman
- Laurent F. Thomas
- Raymond Noordam
- Christian Benner
- Padhraig Gormley
- Ville Artto
- Karina Banasik
- Anna Bjornsdottir
- Dorret I. Boomsma
- Ben M. Brumpton
- Kristoffer Sølvsten Burgdorf
- Julie E. Buring
- Mona Ameri Chalmer
- Irene de Boer
- Martin Dichgans
- Christian Erikstrup
- Markus Färkkilä
- Maiken Elvestad Garbrielsen
- Mohsen Ghanbari
- Knut Hagen
- Paavo Häppölä
- Jouke-Jan Hottenga
- Maria G. Hrafnsdottir
- Kristian Hveem
- Marianne Bakke Johnsen
- Mika Kähönen
- Espen S. Kristoffersen
- Tobias Kurth
- Terho Lehtimäki
- Lannie Lighart
- Sigurdur H. Magnusson
- Rainer Malik
- Ole Birger Pedersen
- Nadine Pelzer
- Brenda W. J. H. Penninx
- Caroline Ran
- Paul M. Ridker
- Frits R. Rosendaal
- Gudrun R. Sigurdardottir
- Anne Heidi Skogholt
- Olafur A. Sveinsson
- Thorgeir E. Thorgeirsson
- Henrik Ullum
- Lisanne S. Vijfhuizen
- Elisabeth Widén
- Ko Willems van Dijk
- Arpo Aromaa
- Andrea Carmine Belin
- Tobias Freilinger
- M. Arfan Ikram
- Marjo-Riitta Järvelin
- Olli T. Raitakari
- Gisela M. Terwindt
- Mikko Kallela
- Maija Wessman
- Jes Olesen
- Daniel I. Chasman
- Dale R. Nyholt
- Hreinn Stefánsson
- Kari Stefansson
- Arn M. J. M. van den Maagdenberg
- Thomas Folkmann Hansen
- Samuli Ripatti
- John-Anker Zwart
- Aarno Palotie
- Matti Pirinen
1 Application
| Application ID | Title |
|---|---|
| 22627 | Fine-mapping genotype-phenotype associations |
Enabling scientific discoveries that improve human health